EVOLUTION OF NEUROTRANSMITTER RECEPTORS

我们的目的是检查结构和功能的演变 神经递质受体蛋白。使用毒扁豆碱、胆碱能和β 肾上腺素能受体作为初始模型系统，我们已经分离和 这些受体的特点是来自大脑和心脏的各种 物种的。大脑和心脏组织都是从所有脊椎动物身上提取的 包括哺乳动物、鸟类、爬行动物、两栖动物、鱼类以及 来自低等物种，包括昆虫(果蝇)。来自毒枭的数据 受体研究表明，在所有研究的参数中(SDS 凝胶相对分子质量、等电点、单抗交叉 反应性、激动剂亲和力、拮抗剂亲和力、立体特异性 配体结合、激动剂亲和力的GTP位移和受体密度) 受体密度似乎已经在9亿年前发生了变化 高等物种的进化逐渐增强。相比之下，Beta版 受体结构在过去似乎发生了更大的变化。 4亿年前。 从人脑、大鼠脑和脑中提纯M受体 心、猪心和鲨鱼的脑和心，以便比较初级 详细的结构。毒鼠强与毒鼠强的进化关系 胆碱能受体和其他神经递质受体也 学习。蛋白质序列数据和定义的基因探针将用于 跟踪肾上腺素能、胆碱能和GABA能受体的演变。 神经递质生物合成/降解酶已经用 受体特异性的单抗。此外，初级序列 这些蛋白质的数据已经与神经递质的数据进行了比较。 任何进化或结构关系的受体蛋白。基因 肾上腺素能和胆碱能受体的克隆正在广泛进行 多种物种用来研究与此相关的特定受体结构域 起到与其他膜效应器的配体结合和偶联的作用。

Our purpose is to examine the structural and functional evolution of neurotransmitter receptor proteins. Using muscarinic cholinergic and beta adrenergic receptors as the initial model systems we have isolated and characterized these receptors from the brains and hearts of a wide variety of species. Brain and heart tissue have been obtained from all vertebrate classes including mammals, birds, reptiles, amphibians, and fish as well as from lower species including insects (Drosophila). Data from muscarinic receptor studies demonstrate that out of all of the parameters studied (SDS gel molecular weight, isoelectric point, monoclonal antibody cross reactivity, agonist affinity, antagonist affinity, stereospecificity of ligand binding, GTP shifts of agonist affinity, and receptor density) only receptor density appears to have changed over 900 million years of evolution gradually increasing in higher species. In contrast, beta receptor structure has appeared to change more dramatically over the past 400 million years. Muscarinic receptors are being purified from human brain, rat brain and heart, pig heart and shark brain and heart in order to compare primary structures in detail. The evolutionary relationship between muscarinic cholinergic receptors and other neurotransmitter receptors is also being studied. Protein sequence data and defined gene probes will be employed to follow the evolution of adrenergic, cholinergic and GABAergic receptors. Neurotransmitter biosynthetic/degradative enzymes have been examined using receptor-specific monoclonal antibodies. In addition, primary sequence data for these proteins has been compared with that of neurotransmitter receptor proteins for any evolutionary or structural relationships. Gene cloning of adrenergic and cholinergic receptors is underway from a wide variety of species to study specific receptor domains involved in such functions as ligand binding and coupling to other membrane effectors.